1. Field of the Invention
The present invention relates to a novel optically active phosphine compound, a transition metal complex including the same phosphine compound as a ligand and a transition metal catalyst useful for a variety of asymmetric synthetic reactions.
2. Description of the Related Art
There have hitherto been many reports on transition metal complexes which can be utilized for asymmetric syntheses such as asymmetric hydrogenations, asymmetric isomerizations, asymmetric hydrosilylations, asymmetric Heck reactions, asymmetric hydroborations and the like. Inter alia, complexes in which transition metal complexes such as ruthenium, rhodium, iridium, palladium and the like are coordinated with an optically active phosphine compound are potent catalysts for asymmetric reactions and some of the catalysts have been used for industrialization. (Asymmetric Catalysis in Organic Synthesis, Ed., R. Noyori, Wiley and Sons, New York (1994)). One of these ligands is a phospholane type compound. The phospholane compound when used as a ligand for a transition metal is useful for asymmetric syntheses such as asymmetric hydrogenations. (Document (A) WO91/17998, document (B) WO93/01199).
However, the phospholane type ligands described in documents (A) and (B) have an optically active phospholane ring structure, and a preparation of the phospholane ring needs expensive optically active 1,4-diols. The preparation of said 1,4-diols requires a special process and equipment (e.g., an electrochemical reaction such as a xe2x80x9cKolbe Reactionxe2x80x9d), which makes industrialization difficult. Additionally, selectivities (diastereoselectivity, enantioselectivity) and catalytic activities of said phospholane ligands are not sufficient depending upon the reaction and reaction substrate and, thus, an improvement in a catalyst is occasionally demanded.
Accordingly, an object of the present invention is to provide a novel phosphine compound having excellent performance (diastereoselectivity, enantioselectivity, catalytic activity) as a ligand of catalysts for asymmetric reactions, in particular, asymmetric hydrogenation reactions. Furthermore, an object of the present invention is to provide an inexpensive preparation of the novel phosphine compound.
In order to achieve the above objects, the present inventors made extensive studies. As a result, it was found that a transition metal complex coordinated with a novel phosphine compound having a fused ring of a benzene ring and a phospholane ring is effective in an asymmetric hydrogenation reaction. It has also been found that this transition metal complex has excellent catalytic activity and enantioselectivity. The invention has been completed based on this finding.
The present invention will be described in detail below.
One of the phosphine compounds of the present invention is represented by the following general formula (1): 
where R1 is a linear or branched alkyl group having 1 to 5 carbon atoms, R2 and R3 represent independently a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, R4, R5, R6 and R7 represent independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a dialkylamino group where the alkyl has 1 to 5 carbon atoms, and X represents a functional group that forms a stable bond with a phosphorous atom, with the proviso that R4 and R5 or R5 and R6 or R6 and R7 taken together with the carbon atoms to which they are attached optionally form a ring or fused ring.
R1 mentioned above includes a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, or neopentyl group.
As R2 and R3, groups such as a methyl group, ethyl group, n-propyl group, and isopropyl group are mentioned.
Examples of R4, R5, R6, R7 include a halogen atom such as fluorine, chlorine, bromine, and iodine; an alkyl group having 1 to 5 carbon atoms, such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, and neopentyl group; an alkoxy group having 1 to 5 carbon atoms, such as a methoxy group, ethoxy group, n-propoxy group, isopropoxy group, and tert-butoxy group; and a dialkylamino group where the alkyl has 1 to 5 carbon atoms, such as dimethylamino group, diethylamino group, pyrrolidino""group, and piperidino group.
Furthermore, the above-described ring or fused ring is a five to ten membered saturated or unsaturated ring such as a benzene ring, cyclopentene ring, cyclohexene ring, cyclopentadiene ring, indene ring, naphthalene ring, or heterocyclic ring such as a methylenedioxy ring system, ethylenedioxy ring system, or trimethylenedioxy ring system.
Specific examples of X are an alkyl group having 1 to 36 carbon atoms which may have a substituent, an aralkyl group, an aryl group which may have a substituent, a heterocyclic group, an alkoxy group, and an amino group. The substituent can be an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a haloalkyl group having 1 to 5 carbon atoms, a halogen atom, an amino group, a mono alkylamino group and a dialkylamino group. Further, the alkyl group having 1 to 5 carbon atoms and alkoxy group having 1 to 5 carbon atoms can be any of those as described above.
Preferred specific examples of X are phenyl groups which may have a substituent, such as a phenyl group, 3-methoxyphenyl group, 3,4-methylenedioxyphenyl group, 1-naphthyl group, 2-naphthyl group, 3,5-di(tert-butyl)-4-methoxyphenyl group, 2-(diphenylphosphino) phenyl group, 2-(di(4-tolyl)phosphino)phenyl group, 2-(di(3,5-xylyl)phosphino)phenyl group, 2-(bis(3,5-di(tert-butyl)-4-methoxyphenyl)phosphino)phenyl group, 2-(di(1-naphthyl)phosphino)phenyl group, 2-(di(2-naphthyl)phosphino)phenyl group, 6-methoxy-2-(diphenylphosphino)phenyl group, and 5,6-methylenedioxy-2-(diphenylphosphino)phenyl group.
Another compound of the present invention is represented by the following general formula (2): 
where R1-R7 are as defined above, R11 is a linear or branched alkyl group having 1 to 5 carbon atoms, R21 and R31 represent independently a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. R41, R51, R61 and R71 represent independently a hydrogen atom, a halogen atom, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a dialkylamino group where the alkyl has 1 to 5 carbon atoms, and Y represents a functional group that forms a stable bond with phosphorous with the proviso that R41 and R51 or R51 and R61 or R61 and R71 taken together with the carbon atoms to which they are attached optionally form a ring or a fused ring.
R11 mentioned above includes a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, and neopentyl group.
As R21 and R31, groups such as a methyl group, ethyl group, n-propyl group, isopropyl group are mentioned.
Examples of R41, R51, R61, R71 include a halogen atom, such as fluorine, chlorine, bromine, and iodine; an alkyl group having 1 to 5 carbon atoms, such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, tert-butyl group, n-pentyl group, isopentyl group, and neopentyl group; an alkoxy group having 1 to 5 carbon atoms, such as a methoxy group, ethoxy group, n-propoxy group, isopropoxy group, and tert-butoxy group; a dialkylamino group where the alkyl has 1 to 5 carbon atoms, such as a dimethylamino group, diethylamino group, pyrrolidino group, and piperidino group.
Furthermore, the above-described ring or fused ring is a five to ten membered saturated or unsaturated ring represented by a benzene ring, cyclopentene ring, cyclohexene ring, cyclopentadiene ring, indene ring, naphthalene ring, and heterocyclic ring including a methylenedioxy ring system, ethylenedioxy ring system, or trimethylenedioxy ring system.
Specific examples of Y are an alkylene group having 1 to 36 carbon atoms which may have substituent(s), an arylene group which may have substituent(s), a divalent heterocyclic group, xe2x80x94Oxe2x80x94R13xe2x80x94Oxe2x80x94, xe2x80x94Oxe2x80x94R14xe2x80x94, xe2x80x94NR23xe2x80x94R15xe2x80x94, xe2x80x94NR24xe2x80x94R16xe2x80x94NR25xe2x80x94, xe2x80x94NR26xe2x80x94R17xe2x80x94Oxe2x80x94, (wherein R13-R17 represent independently an alkylene group having 1 to 36 carbon atoms which may have substituent(s), and an arylene group; and wherein R23xe2x80x94R26 represent independently a hydrogen atom and an alkyl group having 1 to 5 carbon atoms; and a divalent group having an alkylene structure and an arylene structure which may have substituent(s).
Specific examples of the divalent heterocyclic group are pyridine-2, 6-diyl (str. A) and phosphabenzene-2,6-diyl (str. B). 
Further, specific examples of the divalent group having an alkylene structure and an arylene structure which may have substituent(s) are toluene-xcex1,2-diyl group (str. C), ethylbenzene-xcex2,2-diyl (str. D), o-xylene-xcex1,xcex1xe2x80x2-diyl (str. E). 
Preferred specific examples of Y are a phenylene group which may have substituent(s), and an alkylene group which may have substituent(s); more preferred examples are 1,2-phenylene group, 3-methoxy-1,2-phenylene group, 3,4-methylenedioxy-1,2-phenylene group, methylene group, ethylene group, trimethylene group, tetramethylene group, pentamethylene group, and hexamethylene group; and most preferred examples are 1,2-phenylene group, methylene group, and ethylene group.
The present invention includes racemic compounds, meso form compounds and optically active compounds of the aforementioned compounds. Preferred compounds of the aforementioned compounds are compounds where R2, R3, R21, R31 are a hydrogen atom, and more preferred compounds are compounds where R2, R3, R4, R5, R6, R7, R21, R31, R41, R51, R61, R71 are a hydrogen atom.
A process for preparing the compounds of the present invention will be described below. In order to avoid complexity, a representative embodiment of a process for preparing the present compounds is explained by referring to a optically active and (+)-form compound of the following formula (3) ((+)-1,2-bis(2-isopropyl-2,3-dihydro-1H-phosphindol-1-yl)benzene) (hereinafter referred to as xe2x80x9c(+)-iPr-BeePHOS in some cases) among the compounds included in the present invention. However, the present invention is not limited thereto. 
That is, 2-fluorophenylacetic acid (4) and 1,1xe2x80x2-carbonyldiimidazole (CDI) are reacted, followed by treatment with ethyl methylmalonate mono potassium salt in the presence of magnesium chloride to obtain ethyl 4-(2-fluorophenyl)-2-methyl-3-oxobutyrate (5).
The thus obtained compound (5) is asymmetrically hydrogenated using ((R)xe2x80x94SEGPHOS(trademark))-Ru complex to obtain optically active ethyl 4-(2-fluorophenyl)-3-hydroxy-2-methylbutyrate (6) as a mixture of diastereomers.
(SEGPHOS):
((5,6),(5xe2x80x2,6xe2x80x2)-bis(methylenedioxy)biphenyl-2,2xe2x80x2-diyl)bis(di phenylphosphine))
Then, compound (6) is reduced with lithium aluminum hydride to obtain diol (7).
Further, the primary hydroxyl group of the diol (7) is tosylated, and reduction of the tosylate (8) with lithium aluminum hydride gives (+)-1-(2-fluorophenyl)-3-methylbutan-2-ol (9).
After alcohol (9) is mesylated to obtain mesylate (10), 1,2-bisphosphinobenzene is treated successively with n-butyl lithium, mesylate (10) and n-butyl lithium to obtain (+)-1,2-bis(2-isopropyl-2,3-dihydro-1H-phosphindol-1-yl)benzene (+)-(3) as a single diastereomer.
The compound (+)-(3) is produced by the process shown in the following reaction scheme 1. 
In addition, compound (xe2x88x92)-(3) can be obtained by using (S)-SEGPHOS(trademark) instead of (R)-SEGPHOS(trademark). Further, other optically active phosphine ligands may be used instead of SEGPHOS(trademark). Furthermore, generally known transition metal complex for asymmetric synthesis can be used.
Among the present compounds, inter alia, the optically active compound (3) can be obtained from racemic compound (3) using HPLC equipped with an optically active column.
Further, optically active compound (3) can be obtained in a manner that racemic compound (3) is oxidized to the corresponding diphosphine oxide, the enantiomer is optically resolved by an optically active column, followed by reduction of the resolved diphosphine oxide with silane compound.
Additionally, optically active alcohol (9) can be obtained by optical resolution of racemic alcohol (9) by an enzyme.
Phosphines of the present invention represented by the general formula (1) may be obtained by using the corresponding primary phosphine instead of 1,2-bisphosphinobenzene in [SCHEME 1]. Examples of such corresponding primary phosphines are as follows:
Phenylphosphine, 3-methoxyphenylphosphine, 3,4-methylenedioxyphenylphosphine, 1-naphthylphosphine, 2-naphthylphosphine, 3,5-di(tert-butyl)-4-methoxyphenylphosphine 2-(diphenylphosphino)phenylphosphine, 2-(di(4-tolyl)phosphino)phenylphosphine, 2-(di(3,5-xylyl)phosphino)phenylphosphine, 2-(bis(3,5-di(tert-butyl)-4-methoxyphenyl)phosphino)phenylphosphine, 2-(di(1-naphthyl)phosphino)phenylphosphine, 2-(di(2-naphthyl)phosphino)phenylphosphine, 6-methoxy-2-(diphenylphosphino)phenylphosphine, and 5,6-methylenedioxy-2-(diphenylphosphino)phenylphosphine.
Phosphines of the present invention represented by the general formula (2) may be obtained by using the corresponding primary diphosphine instead of 1,2-bisphosphinobenzene in [SCHEME 1]. Examples of such corresponding primary diphosphines are as follows:
3-Methoxy-1,2-bisphosphinobenzene, 3,4-methylenedioxy-1,2-bisphosphinobenzene, 1,1-bisphosphinomethane, 1,2-bisphosphinoethane 1,3-bisphosphinopropane, 1,4-bisphosphinobutane, 1,5-bisphosphinopentane.
On the other hand, phosphines of the present invention represented by the general formula (1) or (2) may be obtained by using the corresponding alcohol instead of compound (9) in [SCHEME 1]. Examples of such corresponding alcohols are as follows:
1-(2-fluorophenyl)propane-2-ol;
1-(2-fluorophenyl)butan-2-ol;
3-(2-fluorophenyl)butan-2-ol;
3-(2-fluorophenyl)-3-methylbutan-2-ol;
2-(2-fluorophenyl)pentan-3-ol;
2-(2-fluorophenyl)-4-methylpentan-3-ol; and
2-(2-fluorophenyl)-2,4-dimethylpentan-3-ol.
Among the compounds of the invention, phosphine compounds represented by the general formula (1) or (2), and, in particular, the optically active compounds represented by the formula (1) or (2), are useful as a ligand of the transition metal complex of the present invention. The following will explain the transition metal complex of the invention. One of the transition metal complexes of the invention is represented by the general formula (31):
MmLnWpUqxe2x80x83xe2x80x83(31) 
(wherein M is transition metal selected from the group consisting of Ir, Rh, Ru, Pd and Ni, and L represents a phosphine compound of the present invention represented by the above general formula (1) as one molecule or two molecules, or a phosphine compound represented by the general formula (2): and with regard to W, U, m, n, p, and q,
when M is Ir or Rh, W is Cl, Br, or I, and m=n=p=2 and q=0,
when M is Ru, (i) W is Cl, Br, or I, U represents a trialkylamino, and m=n=2, p=4, and q=1, (ii) W is Cl, Br, or I, U represents a pyridyl group or a ring substituted pyridyl group, and m=n=1, p=2, and q=2, or (iii) W is a carboxylate group, and m=n=1, p=2, and q=0, (iv) W is Cl, Br, or I, and m=n=p=2 and q=0, or (v) W is Cl, Br or I and U represents a dialkyl ammonium ion, and m=n=2, p=5 and q=0,
when M is Pd, (i) W is Cl, and m=n=1, p=2, and q=0 or (ii) W is allyl group, and m=n=p=2 and q=0, and
when M is Ni, W is Cl, Br, or I, and m=n=1, p=2 and q=0)
In the above complex, the substituent for the pyridyl ring includes an alkyl group having 1 to 3 carbon atoms, a halogen atom, or the like. Moreover, the carboxylate group includes CH3COO, CH3COCH2COO, and the like.
Another one of the transition metal complexes of the invention is represented by the general formula (32):
[MmLnWpUq]Zsxe2x80x83xe2x80x83(32) 
(wherein M is a transition metal selected from the group consisting of Ir, Rh, Ru, Pd, and Ni and L represents a phosphine compound represented by the general formula (1) or (2); and
with regard to W, U, Z, m, n, p, q, and s, when M is Ir, or Rh, W is 1,5-cyclooctadiene or norbornadiene, Z is BF4, ClO4, OTf, PF6, SbF6, or BPh4, and m=n=p=s=1 and q=0, or m=1, n=2, p=q=0 and s=1,
when M is Ru, (i) W is Cl, Br, or I, U represents an aromatic compound or olefin compound which is a neutral ligand, Z is Cl, Br, 1,13, or a sulfonate, and m=n=p=s=q=1 or (ii) Z is BF4, ClO4, OTf, PF6, SbF6, or BPh4, and m=n=1, p=q=0, and s=2)
In the above complex, the aromatic compound as the neutral ligand includes benzene, p-cymene, or the like, and the olefin compound includes 1,5-cyclooctadiene, norbornadiene, or the like.
These transition metal complexes can be produced by a known method. By the way, with regard to the symbols used in the formulae shown in the following transition metal complexes, L represents an optically active compound among the compounds of the invention represented by the general formula (1) as one molecule or two molecules, or represented by the general formula (2) of the invention, cod represents 1,5-cyclooctadiene, nbd represents norbornadiene, Ph represents phenyl group, and Ac represents acetyl group.
Rhodium Complex:
As a specific example of producing a rhodium complex, the complex can be synthesized by reacting bis(cod)rhodium (I) tetrafluoroborate salt with phosphine compound (1) or (2) of the present invention according to the method described in xe2x80x9c4 th edition Jikken Kagaku Koza (Lecture of Experimental Chemistry)xe2x80x9d (Organic Metal Complexes, Vol. 18, pp. 339-344, 1991, edited by the Chemical Society of Japan, published by Marauzen).
The following can be mentioned as specific examples of the rhodium complex.
[Rh(L)Cl]2, [Rh(L)Br]2, [Rh(L)I]2, [Rh(cod)(L)]OTf, [Rh(cod)(L)]BF4, [Rh(cod)(L)]ClO4, [Rh(cod)(L)]SbF6, [Rh(cod)(L)]PF6, [Rh(cod)(L)]BPh4, [Rh(nbd)(L)]OTf, [Rh(nbd)(L)]BF4, [Rh(nbd)(L)]ClO4, [Rh(cod)(L)]SbF6, [Rh(nbd)(L)]PF6, [Rh(nbd)(L)]BPh4, [Rh(L)2]ClO4, [Rh(L)2]OTf, [Rh(L)2]BF4, [Rh(L)2]PF6, [Rh(L)2]SbF6, [Rh(L)2]BPh4 
Ruthenium Complex:
As the method for producing a ruthenium complex, for example, the complex can be prepared by heating [Ru(cod)Cl2]n and BeePHOS under reflux in the presence of triethylamine in toluene solvent as described in the literature (T. Ikariya et al., J. Chem. Soc., Chem. Commun., 922(1988)). Moreover it can also be prepared by heating [Ru(p-cymene)I2]2 and BeePHOS under stirring in methylene chloride and ethanol according to the method described in the literature (K. Mashima et al, J. Chem. Soc., Chem. Commun., 1208 (1989)). The following can be mentioned as specific examples of the ruthenium complex.
Ru(OAc)2(L), Ru(OCOCF3)(L), Ru2Cl4(L)2NEt3, [{RuCl(L)}2(xcexc-Cl)3][Me2NH2], [{RuCl(L)}2(xcexc-Br)3][Me2NH2], [{RuCl(L)}2(xcexc-I)3][Me2NH2], [{RuCl(L)}2(xcexc-Cl)3][Et2NH2], [{RuCl(L)}2(xcexc-Br)3][Et2NH2], [{RuCl(L)}2(xcexc-I)3][Et2NH2], RuCl2 (L), RuBr2(L), RuI2(L), RuCl2(L)(pyridine)2, RuBr2(L)(pyridine)2, RuI2(L)(pyridine)2, [RuCl(benzene)(L)]Cl, [RuBr(benzene)(L)]Br, [RuI(benzene)(L)]I, [RuCl(p-cymene)(L)]Cl, [RuBr(p-cymene)(L)]Br, [RuI(p-cymene) (L)]I, [Ru(L)](OTf)2, [Ru(L)](BF4)2, [Ru(L)](ClO4)2, [Ru(L)](SbF6)2, [Ru(L)](BF4)2 
Iridium Complex:
For example, the iridium complex can be prepared by reacting BeePHOS and an iridium compound, such as [Ir(cod)(CH3CN)]BF4 in tetrahydrofuran according to the method described in the literature (K. Mashima et al, J. Organomet. Chem., 428, 213 (1992)). The following can be mentioned as specific examples of the iridium complex.
[Ir(L)Cl]2, [Ir(L)Br]2, [Ir(L)I]2, [Ir(cod)(L)]OTf, [Ir(cod)(L)]BF4, [Ir(cod)(L)]ClO4, [Ir(cod)(L)]SbF6, [Ir(cod)(L)]PF6, [Ir(cod)(L)]BPh4, [Ir(nbd)(L)]OTf, [Ir(nbd)(L)]BF4, [Ir(nbd)(L)]ClO4, [Ir(cod)(L)]SbF6, [Ir(nbd)(L)]PF6, [Ir(nbd)(L)]BPh4, IrCl(cod)(CO)(L), IrBr(cod)(CO)(L), IrI(cod)(CO)(L), [Ir(L)2]ClO4, [Ir(L)2]OTf, [Ir(L)2]BF4, [Ir(L)2]PF6, [Ir(L)2]SbF6, [Ir(L)2]BPh4 
Palladium Complex:
For example, the palladium complex can be prepared by reacting BeePHOS and a xcfx80-allylpalladium compound according to the method described in a literature (Y. Uozumi et al, J. Am. Chem. Soc., 113, 9887 (1991)). The following can be mentioned as specific examples of the palladium complex.
PdCl2(L), PdBr2(L), PdI2(L), Pd(OAc)2(L), Pd(OCOCF3)2(L), [(xcfx80-allyl)Pd(L)]Cl, [(xcfx80-allyl)Pd(L)]Br, [(xcfx80-allyl)Pd(L)]I, [(xcfx80-allyl)Pd(L)]OTf, [(xcfx80-allyl)Pd(L)]BF4, [(xcfx80-allyl)Pd(L)]ClO4, [(xcfx80-allyl)Pd(L)]SbF6, [(xcfx80-allyl)Pd(L)]PF6, [(xcfx80-allyl)Pd(L)]BPh4, [Pd (L)](OTf)2, [Pd(L)](BPh4)2, [Pd(L)](PF6)2, [Pd(L)](ClO4)2, [Pd(L)](BF4)2, [Pd(L)](SbF6)2, PhCH2Pd(L)Cl, PhCH2Pd(L)Br, PhCH2Pd(L)I, PhPdCl(L), PhPdBr(L), PhPdI(L)
Nickel Complex:
The nickel complex can be prepared by the method described in xe2x80x9c4 th edition Jikken Kagaku Koza (Lectured of Experimental Chemistry)xe2x80x9d, vol. 18, Organic Metal Complexes, 1991, Maruzen, p. 376, edited by the Chemical Society of Japan, or by dissolving BeePHOS and nickel chloride in a mixed solvent of 2-propanol and methanol and heating them under stirring according to the method described in a literature (Y. Uozumi et al, J. Am. Chem. Soc., 113, 9887 (1991)). The following can be mentioned as specific examples of the nickel complex. NiCl2(L), NiBr2(L), NiI2(L)
The transition metal complex containing an optically active phosphine compound of the present invention as a ligand is a useful catalyst for asymmetric synthesis, such as asymmetric hydrogenation, asymmetric isomerization, asymmetric hydroformylation. Racemic modification of compound (1) and (2) is useful as an intermediate of the corresponding optically active compound. In the case of using the complex as a catalyst, the complex may be used after being purified or without purification thereof.
Thus, the novel phosphine compounds of the present invention are useful as, in particular, a ligand for a transition metal complex. Further, a transition metal complex containing said phosphine compound as a ligand is useful catalyst for asymmetric hydrogenation. This novel phosphine compound, useful as ligand, can be produced by a comparatively moderate method. In addition, an asymmetric hydrogenated product can be obtained with high yield and high optical purity by using this catalyst, and in an extremely industrially useful method.
The following Examples and Use Example further illustrate the present invention in detail but are not to be construed as limiting the scope thereof.